Explore the optimal concentration of ADDLs to induce neuron damage in AD model

Alzheimer's disease is a fatal neurodegenerative disease whose principal clinical symptoms are cognitive ability and memory loss. The main pathological features of Alzheimer's disease are the formation of senile plaques in the brain, loss of neurons and synapses, tangles of neurofibrillary abnormal accumulation and reduction of cholinergic neurotransmitter. Aβ is used to be neurotoxin in AD model in vitro. However, Aβ-derived ligand dispersion (ADDLs) is dispersed throughout the brain and not aggregated into plaques soluble oligomers, whose neurotoxic is far stronger than the Aβ. To explore the optimal concentration of ADDLs to induce neuron damage in AD model, primary cortical neurons were isolated from one day old SD rats then cells were treated with ADDLs ( 125 nM, 250 nM, 500 nM and 1000 nM ) for 24 hrs in the 6th day. MTT results showed that ADDLs at concentration of 250 nM, 500 nM and 1000 nM reduced cortical neurons to 66.3%, 65.9% and 58.7% respectively. Microtubuleassociated protein 2 (MAP2) takes part in neuronal morphogenesis. Immunofluorescence results showed that neurite in MAP2 positive neurons appeared beaded lesions, retracted and tapered in dose-effect relationship after the treatment of ADDLs. Based on above results, 250 nM ADDLs is the optimal concentration to induce neuron damage in AD model.